Introduction of a novel nano sized n-sulfonated br?nsted acidic homogeneous catalyst for the promotion of the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-Triones

Article abstract of DOI:10.1166/jnn.2018.13922

In this research work, 4,4-(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium) tetrachloride (NS-C4(DABCO-SO3H)2 ·4Cl) as a new nano-sized N-sulfonic acid was prepared and characterized using different types of spectroscopic methods incl

Full text of DOI:10.1166/jnn.2018.13922

Article
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Nanoscience and Nanotechnology
Vol. 18, 591–603, 2018
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Introduction of a Novel Nano Sized N-Sulfonated
Brönsted Acidic Homogeneous Catalyst for the
Promotion of the Synthesis of
2H-Indazolo[2,1-b]Phthalazine-1,6,11(13H)-Triones
Omid Goli-Jolodar, Farhad Shirini∗, and Mohadeseh Seddighi
Department of Chemistry, College of Science, University of Guilan, Rasht, 41335, Post Box: 1914, I. R. Iran
In this research work, 4,4ꢀ-(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium)
tetrachloride (NS-C4(DABCO-SO3H)2 ·4Cl) as a new nano-sized N-sulfonic acid was prepared and
1
characterized using different types of spectroscopic methods including FT-IR, H NMR, 13C NMR,
XRD, TGA and SEM analysis. This new reagent was efficiently used as catalyst for the promo-
tion of the one-pot synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13Hꢀ-triones derivatives, as a
class of biologically active compounds with important pharmaceutical properties, under solvent-free
conditions during short reaction times in high yields.
Keywords: Nano Brönsted Acidic Catalyst, N-Sulfonic Acids, 2H-Indazolo[2,1-b]
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Phthalazine-1,6,11(13Hꢀ-Triones, Solvent-Free Conditions.
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1. INTRODUCTION
pharmaceuticals, agrochemicals and functional materials
are becoming more and more important.4–10 Among a
large variety of nitrogen-containing heterocyclic com-
pounds, phthalazine derivatives that comprise two bridge-
head nitrogen atoms in a fused ring system have attracted
considerable attention because they show very impor-
tant biological and pharmacological activities includ-
ing anticonvulsant, cardio tonic, vasorelaxant, cytotoxic,
antimicrobial, antifungal, anticancer and anti-inflammatory
activities.11–21 Furthermore, these compounds exhibit good
promise as new luminescent materials or fluorescence
probes.22
Nanocatalysis is a rapidly growing field which involves
the use of nanomaterials as catalysts for a variety of
homogeneous and heterogeneous catalysis applications,
because nanoparticle has a large surface-to-volume ratio
compared to bulk materials, which make them to be attrac-
tive candidates for the requested purposes.1 Also use of
Brönsted-acidic catalysts became one of the remarkable
and important branches in catalyst science because of their
unique properties such as ease of handling, storability, sta-
bility to oxygen and water, ease of design and synthesis
and tunability.2 Among the different kinds of Brönsted-
acidic catalysts, N -sulfonic acid ones have designed to
replace solid acids and traditional mineral liquid acids
like sulfuric acid and hydrochloric acid to catalyze chemi-
cal transformations. Furthermore, their polar nature makes
them useful for use under solvent-free conditions.3
2H-Indazolo[2,1-b]phthalazinetriones as the most
important derivatives of phthalazine can be synthe-
sized according to three-component condensation by
reaction of phthalhydrazide, dimedone and aromatic
aldehydes. In view of their biological, industrial and
synthetic importance, a variety of catalysts such as
cyanuric chloride,23 Mg(HSO4ꢀ2,24 iodine,25 H2SO4,26
ceric ammonium nitrate (CAN),27 silica supported poly
phosphoric acid,28 p-toluenesulfonic acid (p-TSA),29
The heterocyclic compounds have many biochemi-
cal and biological advantages that essential to everyday
life. Among them, nitrogen containing heterocycles are
widespread and their applications in biologically active
30
H14[NaP5W30O110]/SiO2 and Melamine trisulfonic acid
∗Author to whom correspondence should be addressed.
(MTSA)31 are used for the promotion of the synthesis
J. Nanosci. Nanotechnol. 2018, Vol. 18, No. 1
1533-4880/2018/18/591/013
doi:10.1166/jnn.2018.13922
591

Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Goli-Jolodar et al.
of these types of compounds. However, many of these
methodologies are associated with one or more disadvan-
tages such as use of expensive catalysts or toxic organic
solvents, strong acidic conditions and harsh reaction
conditions. Therefore, the development of new synthetic
methods for the efficient preparation of these heterocyclic
is an interesting challenge.
as a novel Brönsted acidic catalyst. NS-C4(DABCO-
SO3H)2 · 4Cl showed high efficiency in the synthesis
of
2H-indazolo[2,1-b]phthalazine-1,6,11(13Hꢀ-triones
probably due to its nano size, which led to the large
surface-to-volume ratio compared to bulk catalyst, and
also its high polarity.
2. EXPERIMENTAL DETAILS
2.1. Materials
More recently, we have introduced some N -sulfonic
acidic catalysts which in them a SO3H group is bonded
to a positive nitrogen (N+ꢀ in an organic compound
and/or a porous system. After preparation these com-
pounds were successfully used as catalysts and regents
in organic transformations.32–46 In continuation of these
studies, we have designed and synthesized nano sized 4,4ꢀ-
(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-
1,4-diium) tetrachloride (NS-C4(DABCO-SO3H)2 ·4Cl)
Chemicals were purchased from Fluka, Merck, Aldrich
Chemical Companies. Yields refer to isolated products.
Products were characterized by their physical constants,
comparison with authentic samples and FT-IR. The purity
determination of the substrate and reaction monitor-
ing were accomplished by TLC on silics-gel polygram
SILG/UV 254 plates.
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Figure 1. FT-IR spectra of DABCO (a), [C4(DABCO)2]·2Cl (b) and NS-[C4(DABCO-SO3H)2]·4Cl (c).
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Goli-Jolodar et al.
Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
2.2. Instrumentation
2.4. Synthesis of Nano Sized 4,4ꢀ-(butane-1,4-diyl)
Bis(1-sulfo-1,4-diazabicyclo[2.2.2]
Octane-1,4-diium) Chloride
([NS-C4(DABCO-SO3H)2]·4Cl)
The FT-IR spectra were run on a VERTEX 70 Brucker
company (Germany). Thermogravimetric analyses (TGA)
were performed on TG/DTA6300 Sll-Nonotechnology
Company (Japan). Samples were heated from 25 to
700 C at ramp 10 C/min under N2 atmosphere. Scan-
ning election microphotographs (SEM) were obtained
on a SEM-Philips XL30. Wide-angle X-ray diffrac-
tion (XRD) measurements were performed at room
temperature on a Siemens D-500 X-ray diffractome-
ter (Germany), using Ni-filtered Co-Kꢁ radiation (ꢂ =
0ꢃ15418 nm).
Chlorosulfonic acid (0.66 mL, 10 mmol) was added drop
wise to a solution of C4(DABCO)2 · 2Cl (1.4 g, 5 mmol)
in dry CH2Cl2 (25 mL) over a period of 30 min in an ice
bath. After completion of the addition, the reaction mix-
ture was stirred for 12 h at room temperature. The residue
was washed with dry diethyl ether (3 × 5 mL) and dried
under vacuum to give nano sized 4,4ꢀ-(butane-1,4-diyl)bis
(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium) chloride
([NS-C4(DABCO-SO3H)2ꢀ] · 4Cl) as a white puffy solid
(M.p: 118–120 ꢁC) in 98.7% yield (4.42 g).
ꢁ
ꢁ
2.3. Synthesis of 1,1ꢀ-(butane-1,4-diyl)Bis
(1,4-diazabicyclo[2.2.2]octan-1-ium) Chloride
([C4(DABCO)2ꢄ·2Cl)
2.5. Catalyst Characterization
2.5.1. FT-IR Analysis
1,4-Dichlorobutane (0.547 mL, 5.0 mmol) was added to
a solution DABCO (1.121 g, 10.0 mmol) in dry CH3CN
(50 mL) and stirred for 4 hr. under reflux conditions.
After completion of the reaction the solvent was removed
under vacuum. The white obtained solid was washed
with diethyl ether. After drying at 50 ꢁC 1,1ꢀ-(butane-
1,4-diyl)bis (1,4-diazabicyclo[2.2.2]octan-1-ium)chloride
([C4(DABCO)2] · 2Cl) was obtained as a white solid
in 98.7% yield (1.39 g). The amount of chloride in
[C4(DABCO)2] · 2Cl was determined by potentiometric
The corresponding FT-IR spectra of DABCO,
[C4(DABCO)2] · 2Cl and nano sized [C4(DABCO-
SO3H)2] · 4Cl are presented in Figure 1. Some of the
stretching and bending vibrations in [C4(DABCO)2] · 2Cl
spectrum were reduced or eliminated compared with
DABCO spectrum, probably due to the limitation of
vibrations of the rings.
In the case of NS-[C4(DABCO-SO3H)2]·4Cl, the broad
band between 3250 and 3750 cm−1 that centered at
3422.53 cm−1 can be attributed to the OH stretching of
the SO3H group. NS-[C4(DABCO-SO3H)2] · 4Cl exhib-
IP: 77.78.215.95 On: Wed, 13 Jun 2018 07:08:05
titration method. For this purpose, 10 mL of 0.05 M
Copyright: American Scientific Publishers
[C4(DABCO)2] · 2Cl in water was titrated with 0.55 M
ited other characteristic absorption bands at 1221.27,
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1056.74 and 590 cm−1 which are assigned to the S
O
AgNO3. The change was happened at 17.5 mL of con-
sumed AgNO3. On the basis of these studies it can be
concluded that [C4(DABCO)2] · 2Cl has 2 equivalent of
Cl− per one mol of this reagent.
asymmetric and symmetric stretching, S–OH bending and
symmetric S–O stretching vibrations, respectively. Further-
more the bands at 1399.60, 885.08 and 883.01 cm−1 in
Figure 2. 1H-NMR spectra of [C4(DABCO)2]·2Cl.
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Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Goli-Jolodar et al.
Figure 3. 1H-NMR spectra of NS-[C4(DABCO-SO3H)2]·4Cl.
the NS-[C4(DABCO-SO3H)2]·4Cl can be related to the
could attributed to the chain hydrogens, and two triplet
peaks at 3.04 and 3.34 related to cyclic hydrogens. After
modification of [C4(DABCO)2] · 2Cl with chlorosulfonic
acid and under the influence of the (–SO3H) groups, the
N–SO2 vibrations.41
1
2.5.2. H-NMR and 13C-NMR Analysis
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1H-NMR spectra of [C (DABCO) ] · 2Cl and NS-
peaks of cyclic hydrogens were shifted to the upper ppm.
Copyright: American Scientific Publishers
4
2
Furthermore, the peak of the acidic hydrogens of NS-
[C4(DABCO-SO3H)2] · 4Cl was appeared at 6.39 ppm.
Also the 13C-NMR of NS-[C4(DABCO-SO3H)2]·4Cl
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[C4(DABCO-SO3H)2] · 4Cl are presented in Figures 2
and 3. The spectrum of [C4(DABCO)2] · 2Cl displayed
two broad singlet peaks at 1.73 and 3.41 ppm which
Figure 4. 13C NMR spectra of NS-[C4(DABCO-SO3H)2]·4Cl.
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Goli-Jolodar et al.
Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Figure 5. SEM micrographs of DABCO (a), [C4(DABCO)2]·2Cl (b) and NS-[C4(DABCO-SO3H)2]·4Cl (c).
showed 4 peaks which demonstrated its structure. The
peaks which are related to the corresponding carbons are
with tiny holes (a), after reaction with 1,4-dichlorobutane
and joining together this surface convert to smooth (b),
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finally after the reaction of [C (DABCO) ] · 2Cl with
specified in Figure 4.
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4
2
chlorosulfonic acid the morphology of [C4(DABCO)2] ·
2Cl was completely changed and the particles size was
reduced to the nano scale (c). Both size reductions and
bumpy surface resulted in increase in the surface area of
the catalyst; this increased the catalytic activity of the cat-
alyst in reaction.47
2.5.3. SEM Analysis
The samples of DABCO, [C4(DABCO)2] · 2Cl and nano
sized [C4(DABCO-SO3H)2] · 4Cl were also analyzed by
scanning electron microscopy (SEM), with magnifications
for determination of the particle shape, surface morphol-
ogy and size distribution (Fig. 5). In DABCO surface mor-
phology picture, the sample has tatter and irregular shape
2.5.4. Powder X-ray Diffraction
XRD patterns of DABCO, [C4(DABCO)2] · 2Cl and nano
sized [C4(DABCO-SO3H)2]·4Cl were investigated in com-
parison with each other in a domain of 10–70ꢁ (Fig. 6).
As shown in this figure, the XRD patterns of DABCO
were appeared at 2ꢅ = 16ꢃ7ꢁ, 17.2ꢁ, 18.5ꢁ, 19.4ꢁ, 30.2ꢁ,
30.9ꢁ, 33.15ꢁ, 35.46ꢁ, 41.96ꢁ and 45.24ꢁ while in the XRD
pattern of [C4(DABCO)2]·2Cl the reflections appeared at
2ꢅ = 15ꢃ23ꢁ, 19.43ꢁ, 22.08ꢁ, 27.4ꢁ and 30.16ꢁ and finally,
the XRD pattern of NS-[C4(DABCO-SO3H)2]·4Cl showed
a broad maximum that assigned to amorphous peak at
Table I. XRD data of DABCO, [C4(DABCO)2] · 2Cl and NS-
[C4(DABCO-SO3H)2]·4Cl.
Peak width
Samples
2ꢅ
[FWHM] (degree) Size [nm]
DABCO
19ꢃ39
22ꢃ08
0.157
0.393
1.152
51.37
20.52
7
[C4(DABCO)2]·2Cl
Figure 6. Particle size of NS-[C4(DABCO-SO3H)2]·4Cl obtained from
NS-[C4(DABCO-SO3H)2]·4Cl 19ꢃ4
SEM analysis.
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Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Goli-Jolodar et al.
Scheme 1. Thermal decomposition by dealkylation of the cation via
SN2 reaction.
gravimetric analysis. Figure 8 display a typical TGA and
DTGA spectra for DABCO, [C4(DABCO)2]·2Cl and NS-
[C4(DABCO-SO3H)2] · 4Cl, using weight percent for the
TGA curve and the differential weight for the DTGA
curve. As shown in this figure DABCO is decomposed
before 150 ꢁC but after first and second processes in
[C4(DABCO)2] · 2Cl and NS-[C4(DABCO-SO3H)2] · 4Cl
thermal the stability is increased. This increase can be
caused by hydrogen bonding sites and nearby the positive
and negative sides.
Figure 7. XRD patterns of DABCO (a), [C4(DABCO)2] · 2Cl (b) and
NS-[C4(DABCO-SO3H)2]·4Cl (c).
2ꢅ = 19ꢃ4ꢁ. Furthermore, the size of the particles was mea-
sured in the highest diffraction line via the Scherrer equa-
tion [D = Kꢂ/ꢆꢇcosꢅꢀ], [ꢂ: Cu radiation (0.154178 nm)],
(Table I). As it can be realized in Table I, the size of the
particles were reduced to nano-size that can be caused by
the addition of ionic component, hydrogen bonding sites
and nearby the positive and negative sites. There is a good
accordance between crystallite sizes obtained from XRD
and SEM data (Fig. 7).48
[C4(DABCO)2] · 2Cl shows a thermal decomposition
ꢁ
blew 120 C which is corresponding to loss of the mois-
ture. The large proportion of it underwent degradation in
ꢁ
the range of 244–286 C (Tmax = 277) that can be related
to the thermal decomposition by dealkylation of the cation
via SN2 reaction of the easiest accessible alkyl group
ꢁ
(Scheme 1),49 and 286–420 C (Tmax = 377) for the com-
2.5.5. TGA Analysis
plete decomposition of the compound. In the case of NS-
[C4(DABCO-SO3H)2]·4Cl, the first weight loss appeared
In order to gain insight into the thermal changes of
[C4(DABCO)2] · 2Cl and NS-[C4(DABCO-SO3H)2] · 4Cl
ꢁ
at <120 C attributed to the loss of the moisture contents.
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The second weight loss which started from 210 ꢁC (Tmax
=
systems the thermal stability was probed with thermo
Copyright: American Scientific Publishers
262 ꢁC) can be a result of the thermal decomposition
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of the pendant sulfonic groups. This sulfonated reagent
undergoes intermolecular bonding interactions in the solid
state, leading to the formation of a rigid network struc-
ture which requires higher temperature for decomposition.
120
100
80
TGA gurves
DABCO
[C4(DABCO)2].2Cl
NS-[C4(DABCO-SO3H)2].4Cl
ꢁ
This is confirmed by the third and fourth (356–556 C)
60
decomposition stages. The DTGA-TGA data show that the
NS-[C4(DABCO-SO3H)2]·4Cl catalyst is stable to 210 ꢁC.
40
20
2.5.6. Titration Curve
0
In this experiment a 15 mL solution of nano sized
[C4(DABCO-SO3H)2] · 4Cl (0.1 M) was titrated with
NaOH (0.05 M). The titration was show that, when 63 mL
of the basic solution is added, all the acidic protons are
neutralized. On the other hand Eq. (1), shows that for the
neutralization of each of the acidic protons 30 mL of the
basic solution is needed. On the basis of these studies it
can be concluded that this ionic liquid has two protic pro-
tons with almost the same acidic power.
0
100
200
300
Temp [°C]
400
500
600
–20
[C4(DABCO)2].2Cl
NS-[C4(DABCO-SO3H)2].4Cl
DABCO
0.5
0.005
0
0
–0.5
–1
0
100
200
300
400
500
600
–0.005
–0.01
–0.015
–0.02
–1.5
–2
–0.025
–0.03
M (acid)×V (acid) = M (base)×V (base)
0ꢃ1 (molar)×15 (mL) = 0ꢃ05 (molar)×V (base) (1)
V (base) = 30 mL
–2.5
–3
–0.035
–0.04
–3.5
–0.045
DTGA curves
On the basis of the above mentioned studies, the struc-
ture which is shown in Scheme 2 is selected for the pre-
pared IL.
Figure 8. TGA curves (up) and DTGA curves (down) for
[C4(DABCO)2 ]·2Cl and NS-[C4(DABCO-SO3H)2]·4Cl.
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Goli-Jolodar et al.
Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Scheme 2. Synthesis of NS-[C4(DABCO-SO3H)2]·4Cl.
Table II. Effect of temperature, amount of the catalyst and solvent
on the synthesis of 13-(4-chlorophenyl)-3,3-dimethyl-2,3,4,13-tetrahydro-
1H-indazolo[1,2-b]phthalazine-1,6,1-trione.
reaction was monitored by TLC [n-hexane:ethylacetate
(10:2)]. After completion, the reaction mass was cooled
to room temperature and washed with water for the sep-
aration of the catalyst. The solid product was purified by
re-crystallization in aqueous EtOH (25%). The products
were characterized by comparison of their physical data
with those of known compounds.
Catalyst
Entry amounta
Time
(min) Yield (%)a
Solvent
Temperature
1
2
3
4
5
6
7
8
3
4
5
3
4
5
3
4
5
3
4
5
4
5
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH2Cl2
CH2Cl2
CH2Cl2
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
r.t.
r.t.
r.t.
Reflux
Reflux
Reflux
Reflux
Reflux
90
90
90
60
60
60
90
90
45
45
60
70
75
75
30
30
2.7. Spectral Data for New Compounds
13-(2-Chlorophenyl)-2,3,4,13-tetrahydro-1H-indazolo[1,2-b]
phthalazine-1,6,11-trione (m): White solid.; M.p.: 232–
ꢁ
234 C.; FT-IR (KBr, ꢈ, cm−1ꢀ: 3018, 1662, 1489, 1364,
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9
90
30
87
1
777; H NMR (400 MHz, DMSO-d , ꢉ, ppm): 2.13–2.14
Copyright: American Scientific Publishers
6
10
11
12
13
14
80ꢁC
80 ꢁC
80 ꢁC
100 ꢁC
100 ꢁC
20
14
8
12
8
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(m, 2H, CH2ꢀ, 2.32–2.36 (m, 2H, CH2ꢀ, 3.29–3.45 (m,
2H, CH2ꢀ, 6.61 (s, 1H, CH), 7.27–7.31 (m, 2H, Ar–H),
7.39–7.41 (m, 2H, Ar–H), 7.52–7.54 (m, 1H, Ar–H),
7.09–8.00 (m, 2H, Ar–H), 8.08–8.10 (m, 1H, Ar–H),
8.28–8.30 (m, 1H, Ar–H).
90
96
85
90
Notes: amol%. bIsolated yield.
13-(2-Nitrophenyl)-2,3,4,13-tetrahydro-1H-indazolo
[1,2-b]phthalazine-1,6,11-trione (n): White solid.; M.p.:
ꢁ
248–250 C.; FT-IR (KBr, ꢈ, cm−1ꢀ: 3016, 1730, 1650,
2.6. General Procedure for the Preparation of 2H-
Indazolo[2,1-b]Phthalazine-1,6,11(13H)-Triones
1630, 1600, 1082; 1H NMR (400 MHz, DMSO-d6, ꢉ,
ppm): 2.10–2.17 (m, 2H, CH2ꢀ, 2.33–2.36 (m, 2H, CH2ꢀ,
3.24–3.45 (m, 2H, CH2ꢀ, 7.18 (s, 1H, CH), 7.52–7.56
(1H, td, J1 = 7ꢃ2 Hz, J2 = 1ꢃ2 Hz), 7.61–7.65 (1H, td,
J1 = 7ꢃ2 Hz, J2 = 1ꢃ2 Hz), 7.70–7.72 (2H, dd, J1 = 8ꢃ0 Hz,
J2 = 1ꢃ2 Hz), 7.97–8.01 (m, 3H, Ar–H), 8.07–8.11 (m, 1H,
A mixture of the requested aldehyde (1.0 mmol), dime-
done and/or 1,3-cyclohexadione (1.0 mmol), phthalhy-
drazide (1.0 mmol) and NS-[C4(DABCO-SO3H)2ꢀ] · 4Cl
(0.010 g, 5 mol%) was heated in an oil bath (80 ꢁC)
under solvent-free conditions for the appropriate time. The
Scheme 3. NS-[C4(DABCO-SO3H)2]·4Cl catalyzed the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13Hꢀ-triones derivatives.
J. Nanosci. Nanotechnol. 18, 591–603, 2018
597

Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Goli-Jolodar et al.
Table III. Preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13Hꢀ-triones derivatives using NS-[C4(DABCO-SO3H)2]·4Cl as the catalyst.
M.p. ꢁC
Entry
1
Product
Time (min)
10
Yield (%)a
90
Found
Reported [ref.]
205–20716
(a)
(b)
(c)
(d)
202–203
O
O
N
N
O
O
2
3
4
5
6
7
8
8
89
88
91
254–257
245–247
235–238
180–182
198–200
268–270
257–259
262–26416
242–24326
236–23825
184–18820
206–20825
270–27116
262–26416
Cl
O
N
N
O
17
20
O
O
OMe
O
N
N
O
NO2
O
N
N
O
O
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(e)
20
90
93
94
96
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OH
O
N
N
O
OMe
O
(f)
12
13
8
O
N
N
O
O
NO2
O
(g)
(h)
N
N
O
Cl
O
O
N
N
O
598
J. Nanosci. Nanotechnol. 18, 591–603, 2018

Goli-Jolodar et al.
Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Table III. Continued.
M.p. ꢁC
Entry
9
Product
Time (min)
8
Yield (%)a
95
Found
Reported [ref.]
258–26016
Br
(i)
252–256
O
O
O
O
N
N
10
(j)
12
94
215–217
220–22116
OMe
O
N
N
O
O
NO2
O
11
(k)
15
93
95
217–220
220–22216
N
N
O
O
12
13
14
15
16
(l)
8
220–222
232–234
248–250
222–224
250–255
222–22419
O
N
N
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O
O
(m)
(n)
(o)
(p)
15
18
12
6
93
92
92
93
–
–
Cl
O
N
N
O
O
NO2
O
N
N
O
228–23019
NO2
O
O
N
N
O
19
Cl
–
O
O
N
N
O
J. Nanosci. Nanotechnol. 18, 591–603, 2018
599

Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Table III. Continued.
Goli-Jolodar et al.
M.p. ꢁC
Entry
17
Product
Time (min)
6
Yield (%)a
94
Found
Reported [ref.]
Br
(q)
270–274
279–28220
O
O
O
O
O
N
N
18
19
20
21
(r)
(s)
(t)
8
94
87
93
250–254
240–245
284–285
237–240
254–25519
252–25425
>28027
OMe
O
N
N
NO2
25
30
O
O
O
N
N
CN
O
O
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O
N
N
244–24619
Me
(u)
(v)
(w)
5
90
93
85
O
O
O
O
O
N
N
22
15
259–261
265–26619
OH
O
N
N
23
17
248–251
256–25819
NMe2
O
O
O
N
N
Note: aIsolated yield.
600
J. Nanosci. Nanotechnol. 18, 591–603, 2018

Goli-Jolodar et al.
Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Ar–H), 8.27–8.29 (m, 1H, Ar–H); 13C NMR (100 MHz,
DMSO-d6, ꢉ, ppm): 192.75, 155.87, 154.40, 154.21,
149.28, 135.07, 134.37, 134.13, 131.80, 131.25, 129.78,
129.61, 133.538, 132.547, 132.393, 132.108, 125.427,
63.976, 39.559, 27.569, 25.566.
positions of the aromatic ring of the selected aldehydes
are used to form various products. The ortho Cl, OMe,
NO2 and OH substituted aldehydes are reacted slower
than the same functional groups on the other positions
because of the steric or electronic effects of the sub-
stituents (entries 2–5, 13 and 14). In the same way, the
reaction of 1,3-cyclohexanedione for the synthesis of 2H-
indazolo[1,2-b]phthalazine-triones was examined and the
desired products were obtained in high yields (Table III,
entries 12–23). It should be noted that in the absence of the
catalyst the model reaction produced the requested product
in low yields (<30%) after 3 h (Table IV, entry 1).
In a plausible mechanism at first step, the aldehyde
is activated by the proton from nano sized [C4(DABCO-
SO3H)2] · 4Cl then the carbonyl carbon is attacked by
the nucleophilic cyclohexanedione derivatives to provide
the corresponding Knoevenagel products (I). The follow-
ing addition of the Knoevenagel products to phthalhy-
drazide gives the acyclic adduct intermediate (II), which
undergoes intramolecular cyclization by the participation
of the OH and NH groups to afford the 2H-indazolo[2,1-
b]phthalazine-1,6,11(13Hꢀ-trione derivatives (Scheme 4).
To investigate the recyclability of the catalyst
in the synthesis of 2H-indazolo[2,1-b]phthalazine-
1,6,11(13Hꢀ-trione derivatives the reaction between
4-chlorobenzaldehyde, dimedone and phthalhydrazide
under optimized reaction conditions was investigated
again. When the reaction completed, water was added
to the reaction media and the catalyst was separated by
filtrꢁation. Then the filtrate was dried under vacuum at
70 C to obtain the recycled catalyst and reused for the
same reaction. This procedure was repeated at least for
five runs, and each time the product was obtained by
the recovered catalyst without considerable change in the
reaction time and yield. The results are shown in Figure 9.
In order to show the merit of this method the
efficiency of nano sized [C4(DABCO-SO3H)2] ·
4Cl with the other catalysts in the synthesis of
4-(1,6,11-Trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo
[1,2-b] phthalazin-13-yl)benzonitrile (t): White solid.;
ꢁ
M.p.: 284–285 C.; FT-IR (KBr, ꢈ, cm−1ꢀ: 3018, 2200,
1720, 1655, 1626, 1602, 1080. 1H NMR (400 MHz,
DMSO-d6, ꢉ, ppm): 2.11–2.13 (m, 2H, CH2ꢀ, 2.33–2.36
(m, 2H, CH2ꢀ, 3.21–3.26 (m, 2H, CH2ꢀ, 6.35 (s, 1H,
CH), 7.71–7.73 (d, J = 8 Hz, 2H, Ar–H), 7.79–7.81
(d, J = 8 Hz, 2H, Ar–H), 7.97–8.01 (m, 2H, Ar–H),
8.09–8.11 (m, 1H, Ar–H), 8.28–8.30 (m, 1H, Ar–H).
3. RESULTS AND DISCUSSION
3.1. Catalytic Activity
On the basis of the information obtained from the studies
on the structure of nano sized [C4(DABCO-SO3H)2]·4Cl
it is expected that this reagent can be used as an efficient
catalyst for the promotion of the reactions which need the
use of an acidic catalyst to speed-up. So this reagent was
used in the promotion of the synthesis 2H-indazolo[2,1-
b]phthalazine-1,6,11(13Hꢀ-triones.
At first and for optimization of the amount of
the catalyst and reaction conditions, the reaction of
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4-chlorobenzaldehyde, phthalhydrazide and dimedone was
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studied in the presence of NS-C4(DABCO-SO H)2 · 4Cl
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and the results are arranged in Table II. Using these
data, the optimized conditions are selected as shown in
Scheme 3.
After optimization of the reaction conditions and in
order to show the efficiency of these method differ-
ent types of aldehydes were subjected to the same
reaction under the determined conditions. As shown in
Table III, key functional groups such as halides, alkyl,
nitro, methoxy, and nitrile on the ortho, meta and para
Table IV. Compared performance of various catalysts with NS-C4(DABCO-SO3H)2 ·4Cl in the synthesis of 13-(4-chlorophenyl)-3,3-dimethyl-2,3,4,13-
tetrahydro-1H-indazolo[1,2-b]phthalazine-1,6,11-trione.
Entry
Catalyst (mol%)
Conditions
Time (min)
Yield (%)a
Ref.
b
1
2
3
4
5
6
7
8
–
solvent free/100 ꢁC
Neat/100 ꢁC
3 hr
15
4
10
25
30
120
6
10
7
3 hr
3 hr
8
>30
97
88
92
88
88
90
93
93
–
Cyanuric chloride (3)
Mg(HSO4ꢀ2 (11.5)
Iodine (10)
[23]
[24]
[25]
[26]
[26]
[27]
[28]
[29]
[30]
solvent free/100 ꢁC
sonic bath (35 kHz)
[bmim]BF4/r.t.
H2SO4 (15)
[bmim]BF4 and H2SO4 (15)
CAN (5)
PPA-SiO2 (0.1 g)
p-TSA (30)
H14[NaP5W30O110]/SiO2
DABCO (5)
H2O-EtOH/reflux
PEG/50 ꢁC
solvent free/100 ꢁC
solvent free/80 ꢁC
reflux
9
10
11
12
13
87.5
>30
60
b
solvent free/80 ꢁC
solvent free/80 ꢁC
solvent free/80 ꢁC
–
b
[C4(DABCO)2]·2Cl (5)
–
b
[C4(DABCO-SO3H)2]·4Cl (5)
96
–
Notes: aIsolated yield. bThis work.
J. Nanosci. Nanotechnol. 18, 591–603, 2018
601

Introduction of a Novel Nano Sized N-Sulfonated Brönsted Acidic Homogeneous Catalyst
Goli-Jolodar et al.
Scheme 4. Proposed mechanism for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13Hꢀ-trione derivatives in the presence of
NS-[C4(DABCO-SO3H)2]·4Cl.
13-(4-chlorophenyl)-3,3-dimethyl-2,3,4,13-tetrahydro-1H-
indazolo[1,2-b]phthalazine-1,6,1-trione is compared in
for the synthesis of 2H-indazolo[2,1-b]phthalazine-
1,6,11(13Hꢀ-trione derivatives. The most important advan-
Table IV. As shown in this table, the newly developed
IP: 77.78.215.95 On: Wed,ta1g3esJuonf t2h0is18ca0ta7l:y0s8t :t0h5at can be representing are:
Copyright: American Scientific Publishers
method avoids some of the disadvantages associated
(1) nano-size and high polarity of catalyst,
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with the other procedures such as harsh reaction con-
(2) simplicity in the preparation procedure,
(3) not is harmful for environment,
(4) availability of the starting material and,
(5) ease of handling.
ditions, high temperature, use of toxic or moisture
sensitive catalyst, use of higher amounts of the catalysts
and recoverability of the catalyst. Also DABCO and
[C4(DABCO)2]·2Cl are used to catalyze this reaction, but
after 3 hr the obtained yield was very low (Table IV, entry
11 and 12).
Also, simplicity and easy work-up, high reaction rates,
excellent yields and eco-friendly procedure are the advan-
tages of the present method used for the prepara-
tion of 2H-indazolo[2,1-b]phthalazine-1,6,11(13Hꢀ-trione
derivatives.
4. CONCLUSIONS
In summary, we have introduced
a
novel nano
N -Sulfonic Brønsted acidic catalyst formulated as
C4(DABCO-SO3H)2 ·4Cl as a high-performance catalyst
Acknowledgments: The authors are grateful to the
Guilan University Research Council for the partial support
of this work.
Reusability of the catalyst
run 5
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